Pharmacokinetics 1

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kyleannkelsey
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251255
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Pharmacokinetics 1
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2013-12-06 10:52:14
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Pharmacokinetics
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Pharmacokineticss 1
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  1. What is considered elevated SCr?
    >1.5 mg/dL
  2. For a drug to be approved by the FDA does it need to be tested on renaly insufficient patients?
    Yes
  3. Breakdown of the kidney’s function can be at any point where what is occurring?
    Filtration, Reabsorption, Secretion and Excretion
  4. Absorption can be altered by what parameters (as listed in class)?
    Changes in GI tract, Vomiting or Diarrhea, Antacid use, edema, transit time in GI
  5. (True/False) There are a wealth of absolute bioavailability studies in patients with chronic kidney disease.
    False, there are a limited number
  6. Since there are limited numbers of bioavailability studies in patients with chronic kidney disorders, how can you extrapolate absorption?
    Estimate it, assuming that absorption is slowed or the extent is reduced
  7. What factors can alter Distribution (Vd) in reduced renal function patients?
    ∆ in body composition (like Water), ↑ or ↓ in protein binding or tissue binding
  8. Does the Vd of a drug increase of decrease in end stage renal disease?
    Can either increase or decrease
  9. What drugs would you expect to have an increased Vd in a patient with end stage renal disease?
    Cefazolin, Gentamycin, Vancomycin and Phenytoin
  10. What drugs would you expect to have a decreased Vd in a patient with end stage renal disease and why?
    Digoxin, due to ↓ tissue binding
  11. Why is it important that Dialysate is aqueous in nature?
    Tends to remove drugs that are soluble in aqueous solutions at a higher rate
  12. What type of drugs are removed by Dialysate more readily?
    Water soluble drugs or drugs with a low Vd
  13. What type of drugs are removed by Dialysate less readily?
    Lipid soluble drugs or those with a high Vd
  14. Protein binding of acidic drugs are generally increased or decreased in ESKD?
    Decreased
  15. Protein binding of basic drugs are generally increased or decreased in ESKD?
    Increased or Decreased
  16. (True/False) Serum concentration is representative of how much drug is bound to protein.
    False, need to correct for this value
  17. Clonidine is a basic drug, will it increase or decrease in protein binding in patients with ESKD?
    Increase
  18. Morphine is a basic drug, will it increase or decrease in protein binding in patients with ESKD?
    Decrease
  19. In patients with ESKD, would you expect metabolism to be enhanced or reduced?
    Reduced
  20. What does reduced metabolism in ESKD patients often lead to?
    Accumulation of parent compound or active metabolites
  21. Can CKD reduce non-kidney metabolism?
    Yes
  22. What is the most common drug to have an active metabolite that can accumulate in ESKD patients?
    Demerol
  23. Should Demerol be used in patients with ESKD, why or why not?
    No, has an active metabolite that may accumulate and cause seizures
  24. What aspects of excretion can be altered by ESKD?
    Glomerular filtration, Tubular secretion and Tubular reabsorption
  25. What does the Rate of Excretion =
    Rate of filtration + Rate of secretion – Rate of absorption
  26. Reduction in glomerular filtration rate results in an increased or decreased drug exposure?
    Increased
  27. Describe how Dialysis works:
    Patients own blood and dialysate solution are perfused on opposite sides of a semipermeable membrane, substance are removed from the blood due to diffusion and ultrafiltration
  28. Is the patient’s own blood replaced or returned back to the patient in Dialysis?
    Returned
  29. (True/False) Dialysis can remove drugs at variable rates based on MW.
    True
  30. (True/False) The amount of drug being pumped from a patient on Dialysis can affect the amount of medication removed.
    True
  31. (True/False) The Dialysate pump rate can influence the amount of drug removed from a patient.
    True
  32. (True/False) The ultrafiltration rate for has no effect on the amount of drug removed from a patient on Dialysis.
    False, can effect
  33. (True/False) Peritoneal dialysis pulls off more meds that renal replacement therapies/Dialysis.
    False, pulls off fewer meds
  34. Are small or large MW drugs removed more easily during dialysis?
    Small MW drugs
  35. What is considered a small molecular weight drug?
    <300 daltons
  36. What is considered a medium molecular weight drug?
    300-12,000 daltons
  37. What is considered a large molecular weight drug?
    >12,000 daltons
  38. What type of drugs will have a higher likelihood of needing removal by a convective process ( a diff. setting on the machine)?
    Large MW drugs
  39. (True/False) MW of drugs is usually easily accessible.
    False
  40. (True/False) Generally, only free/unbound drugs can pass through membrane pores on a Dialysis filter.
    True
  41. Define IPD:
    Intermittent Peritoneal Dialysis
  42. Define CAPD:
    Continuous Ambulatory Peritoneal Dialysis
  43. What type of filter would be used for intermittent Hemodialysis?
    High-Fluc dialysis filter or conventional filter
  44. What does CAVHDF or CVVHDF stand for?
    Continuous arteriovenous or venovenous hemodiafiltration
  45. What does CAVH or CVVH stand for?
    Continuous arteriovenous or vevovenous hemofiltration
  46. What are the Continuous Renal Replacement Thereapies?
    CAVHDF/CVVHDF or CAVH/CVVH
  47. How is IPD achieved?
    The patient’s own peritoneal fluids are used to remove electrolytes and toxins
  48. What is the least likely method of Hemodialysis to remove drugs?
    IPD
  49. Would a CRRT method or an intermittent hemodialysis method be set at a higher rate?
    Intermittent
  50. CRRT or IHD remove more medication?
    CRRT
  51. Between the various Hemodiualysis methods, rank them in order of most and least likely to remove mediactions:
    CAVHDF/CVVHDF > CAVH/CVVH > High Flux Filter HD >Conventional Filter HD > IPD > CAPD
  52. A conventional filter hemodialysis can remove drugs with what molecular weight?
    <1000 daltons
  53. A High-Flux filter hemodialysis can remove drugs with what molecular weight?
    >1,000 – 20,000 daltons
  54. A Continuous Renal Replacement Therapies can remove drugs with what molecular weight?
    >5,000 daltons
  55. Would Vancomycin be removed by a Conventional Filter Hemodialysis system, explain?
    No, Vancomycin = 1,500 daltons, Conventional filter only removes <1,000 daltons
  56. Would Vancomycin be removed by a High-Flux Filter Hemodialysis system, explain?
    Yes, Vancomycin = 1,500 daltons, High-Flux Filter Hemodialysis removes >1,000 – 20,000 daltons
  57. Would Aminoglycosides be removed by a Conventional Filter Hemodialysis system, explain?
    Yes, Aminoglycosides = 500 daltons, Conventional filter removes <1,000 daltons
  58. What advantage does a Dialysis membrane with a higher ultrafiltration coefficient (Kuf) have?
    Potential to remove more unbound drug
  59. What are the major variables of a Dialysis membrane?
    Pore size and Ultrafiltration coefficient (Kuf)
  60. (True/False) Dialysate and Blood in a Dialysis machine flow in the same direction.
    False, opposite directions
  61. What does QB stand for?
    Blood flow
  62. What does QD or DFR stand for?
    Dialysate Flow
  63. The faster the QB, the __________ the drug accumulates in the Dialysate.
    Faster
  64. The faster the QD, the__________ the drug is removed from the dialyzer.
    Faster
  65. What biomarkers can be used to quantify Renal plasma/blood flow?
    PAH, 131 I-OIH and [99m]c-MAG3
  66. What biomarkers can be used to quantify Glomerular filtration rate?
    Inulin, Sinstrin, lothalamate, 125I-lothalamate, lohexol, Creatine, Cystatin C, [99m]c-DTPA
  67. What biomarkers can be used to quantify Tubular function?
    PAH, TEA, B2 or A1 microglobulin, RBP, Protein HC, NAG, AAP, ABP
  68. What is the most commonly used biomarker for Glomerular filtration rate?
    Creatinine clearance
  69. Why is Creatinine clearance used preferentially over other biomarker methods?
    It is less labor intensive or expensive
  70. Define Glomerular Filtration Rate:
    Volume of fluid filtered through the glomerular capillaries into the Bowman’s capsule per unit time
  71. Define the Creatinine Clearance rate:
    Volume of blood plasma that is cleared of creatinine per unit time
  72. Serum Creatinine is a product of what?
    Creatine metabolism from muscle
  73. How is Creatinine eliminated?
    Primarily by glomerular filtration
  74. As SCr rises, what happens to the GFR and CrCl?
    Decrease
  75. (True/False) SCr concentration alone is enough to assess the level of kidney function.
    False
  76. (True/False) SCr is influenced be a small number of variable.
    False, many factors weigh in
  77. Why is SCr not sufficient to evaluate kidney function?
    SCr varies with age, etc.
  78. (True/False) eCrCl and eGFR are direct measurement of Renal function.
    False, these equations are estimations
  79. What is a downfall to eCrCl and eGFR measurements?
    Typically validated in patients with STABLE/NORMAL kidney function
  80. Along with ____________, estimations of kidney function using eCrCl and eGFR can be used to guide drug dosing.
    Clinical judgment
  81. What is the most commonly used Creatinine Clearance estimation?
    Cockcroft & Gault
  82. What is the Cockcroft & Gault equation for men?
    CLcr = (140-Age) x kg / (Scr x 72)
  83. What is the Cockcroft & Gault equation for women?
    CLcr = 0.85 x [(140-Age) x kg / (Scr x 72)]
  84. What is a normal range for Creatinine Clearance for a Male?
    97 – 137 ml/min
  85. What is a normal range for Creatinine Clearance for a Female?
    88 – 128 ml/min
  86. What is a normal range for Creatinine Clearance for a Newborn (1 days old)?
    5 – 50 ml/min/1.73 m^2
  87. What is a normal range for Creatinine Clearance for a Newborn (6 days old)?
    15 – 90 ml/min/1.73 m^2
  88. What is the FDA classification of normal renal function based on eGFR or eCrCl?
    >90 ml/min
  89. Why do men have a slightly higher creatinine clearance?
    More muscle mass
  90. Was Cockroft-Gault originally measured in female patients?
    No
  91. For exams in this class, you should use Adjusted BW or Actual body weight for the Cockcroft-Gault equation?
    Actual, unless the patient weighs >20% above IBW then use Adjusted BW (AdjBW)
  92. What is the IBW for men?
    50 kg + 2.3 (inches over 5 ft)
  93. What is the IBW for women?
    45.5 kg + 2.3 (inches over 5 ft tall)
  94. What is the Adjusted BW?
    [0.4 x (Actual BW – IBW)] +IBW
  95. Is it better to use actual SCr or round up to 1 mg/dL for elderly patients when estimating CrCl?
    Better to use Actual
  96. Why is it hypothesized a low elderly person’s SCr should be rounded up to 1mg/dL?
    Compensates for lower muscle mass in elderly (not accurate, don’t do)
  97. What do you need to know about a person to use the MDRD equation?
    SCr, Age, Race and Gender
  98. What is MDRD commonly used for?
    To get a general estimate of whether a patient is at risk for Kidney disease, etc.
  99. Why would a person have an individualized MDRD?
    Obeisity
  100. How is eGFR individualized?
    Multiplied by BSA/1.73
  101. The Schwartz equation is used to estimate kidney finction in what group?
    <18 years

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